Brain in a dish: Neuron cultures offer hope for more effective bipolar treatments

Dr. Martin Alda
Dr. Martin Alda in his Halifax office with the Mogens Schou Award for Research from the International Society for Bipolar Disorders.

It may seem like science fiction to take a person’s cells—from almost any tissue—and turn them into stem cells and then engineer those stem cells into neurons. But this is exactly what researchers at the Salk Institute in California are up to—and NSHA psychiatrist Dr. Martin Alda is working with them, in his quest to better understand and treat bipolar disorder.

“We have found that nerve cells engineered from the cells of people with bipolar disorder are hyperexcitable,” Dr. Alda says. “Their electrical activity is three times higher than the nerve cells engineered from people without the illness.”

Lithium, fortunately, is remarkably successful in stabilizing the disorder— even after years of illness—in about one third of the people who have it. These are the “lithium responders.”

Bipolar disorder is a very serious mental illness characterized by alternating phases of mania and depression. In manic phases, people develop grandiose delusions that can lead to such damaging behaviours as spending or gambling away all of their money. In depressive phases, suicide risk is extremely high.

“When we added lithium to hyper-excited neurons from lithium responders, the electrical activity settled right down,” notes Dr. Alda. “But when we added lithium to the neurons from patients who do not respond, there was no effect.”

While this result is not surprising, it IS powerful. “Now we have an objective way to see if someone is a lithium responder or not,” says Dr. Alda. “This will save a lot of time in trial and error to get people stabilized faster.”

The technology is not yet ready for large-scale use, but Dr. Alda is working with colleagues at the Montreal Neurological Institute to develop a clinical test. And, he’s part of an international consortium that’s developing a platform for high-throughput drug testing.

“We need to identify effective agents for the 70 per cent of bipolar patients who do NOT respond to lithium,” he says. “There are thousands of proven safe agents that have never been tested for bipolar disorder, as well as new agents yet to be discovered or created—now we can test them in a petri dish model of bipolar disorder.”

Such a technology opens the door to the possibility of tailored treatments, literally targeted to an individual’s own particular version of bipolar disorder.

For Dr. Alda—a leading researcher in bipolar disorder for nearly 30 years—this is the kind of breakthrough that could scarcely be imagined even a decade ago.

Now, it is clearly within reach.